Evaluation of children's centres in England (ECCE) : strand 1: first survey of children's centre leaders in the most deprived areas

This report is the first output from the Evaluation of Children's Centres in England (ECCE), a six year study commissioned by the Department for Education and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics. The aim of ECCE is to provide an in-depth understanding of children's centre services, including their effectiveness in relation to different management and delivery approaches and the cost of delivering different types of services. The aim of Strand 1 is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision with which to select centres for subsequent stages of the evaluation and to explore different models of provision. The findings below relate to 500 children's centres that are representative of all phase 1 and 2 centres (i.e. those in the 30percent most deprived areas).</p

Findings from a pilot randomised trial of an asthma internet self-management intervention (RAISIN)

&lt;b&gt;Objective &lt;/b&gt;To evaluate the feasibility of a phase 3 randomised controlled trial (RCT) of a website (Living Well with Asthma) to support self-management.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Design and setting&lt;/b&gt; Phase 2, parallel group, RCT, participants recruited from 20 general practices across Glasgow, UK. Randomisation through automated voice response, after baseline data collection, to website access for minimum 12 weeks or usual care.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Participants &lt;/b&gt;Adults (age≥16 years) with physician diagnosed, symptomatic asthma (Asthma Control Questionnaire (ACQ) score ≥1). People with unstable asthma or other lung disease were excluded.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Intervention&lt;/b&gt; Living Well with Asthma’ is a desktop/ laptop compatible interactive website designed with input from asthma/ behaviour change specialists, and adults with asthma. It aims to support optimal medication management, promote use of action plans, encourage attendance at asthma reviews and increase physical activity.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Outcome measures&lt;/b&gt; Primary outcomes were recruitment/retention, website use, ACQ and mini- Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included patient activation, prescribing, adherence, spirometry, lung inflammation and health service contacts after 12 weeks. Blinding postrandomisation was not possible.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results &lt;/b&gt;Recruitment target met. 51 participants randomised (25 intervention group). Age range 16–78 years; 75% female; 28% from most deprived quintile. 45/51 (88%; 20 intervention group) followed up. 19 (76% of the intervention group) used the website, for a mean of 18 min (range 0–49). 17 went beyond the 2 ‘core’ modules. Median number of logins was 1 (IQR 1–2, range 0–7). No significant difference in the prespecified primary efficacy measures of ACQ scores (−0.36; 95% CI −0.96 to 0.23; p=0.225), and mini-AQLQ scores (0.38; −0.13 to 0.89; p=0.136). No adverse events.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Recruitment and retention confirmed feasibility; trends to improved outcomes suggest use of Living Well with Asthma may improve self-management in adults with asthma and merits further development followed by investigation in a phase 3 trial

Revisiting the Genicular Nerve Block: An Up-to-Date Guide Utilizing Ultrasound Guidance and Peripheral Nerve Stimulation - Anatomy Description and Technique Standardization

Background: Over the last decade, several authors have reported that percutaneous peripheral nerve stimulation (PNS) can be used to assist in verifying the position of the procedure needle tip in relation to nerve structures, and that the combined technique using both ultrasound (US) guidance and PNS may serve as a reliable method for confirmation of the correct position of the procedure needle tip. It has also been reported that, when combined with US guidance, PNS may increase the success rate of pain management interventions. Objectives: The aim of this technical report was to standardize an effective and easy to learn illustrated step-by-step technical approach to nerve identification during US-guided genicular nerve blocks, using percutaneous PNS as a verification instrument for procedure needle tip location. Study design: This technical protocol was developed based on the results of the authors' most recent cadaveric study on the innervation of the knee joint capsule. The technique was developed and tested by 4 different interventionists with different levels of expertise in US-guided procedures. Setting: The cadaveric study of the knee joint capsule innervation was performed at the laboratory of the Division of Anatomy of one institution. The technical protocol using US and PNS was later developed at the medical simulation center of a different institution. Methods: A team of anatomists from a division of anatomy of one institution performed the cadaveric study on the innervation of the knee joint capsule. A team of physicians then developed the step-by-step approach to this technical protocol at the medical simulation center of a different institution. Finally, the illustrated step-by-step approach was tested by 4 different interventionists with different levels of expertise in US-guided procedures (1 beginner-level user; 1 intermediate-level user; 2 expert-level users), using a portable percutaneous PNS and 2 different US transducers at 2 different institutions. Results: This technical protocol was successfully developed based on the results of the cadaveric study on the innervation of the knee joint capsule. Additionally, it was later successfully tested by interventionists with various levels of expertise utilizing different US equipment at separate institutions. Limitations: By combining US and nerve stimulation, this protocol requires the availability of both US equipment and necessary equipment for nerve stimulation that must all be made available in the sterile field. Another potential disadvantage is that nerve stimulation controls and the US image screen are generally located on 2 separate display panels, which could cause difficulty with visualization and simultaneous calibration for 2 individual devices. Conclusions: Our illustrated step-by-step technical protocol can be effectively and safely utilized as a reliable method of training, by which physicians with little to moderate US experience can improve their skills in accurately identifying the genicular nerves while performing US-guided examinations with the intent of executing a peripheral nerve block.info:eu-repo/semantics/publishedVersio

Evaluation of children’s centres in England (ECCE). Strand 1: First survey of children’s centre leaders in the most deprived areas

This is the final version of the report. Available from the Department for Education via the link in this record.The evaluation of children’s centres in England (ECCE) is a 6-year study commissioned by the Department for Education (DfE) and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics. The aim of this report is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision and to explore different models of provision. The profile covers all main aspects of provision including management, staff, services, users and finance and involves nearly 500 children’s centres, representative of all phase 1 and 2 centres in the most disadvantaged area

An Integrated Disease/Pharmacokinetic/Pharmacodynamic Model Suggests Improved Interleukin-21 Regimens Validated Prospectively for Mouse Solid Cancers

Interleukin (IL)-21 is an attractive antitumor agent with potent immunomodulatory functions. Yet thus far, the cytokine has yielded only partial responses in solid cancer patients, and conditions for beneficial IL-21 immunotherapy remain elusive. The current work aims to identify clinically-relevant IL-21 regimens with enhanced efficacy, based on mathematical modeling of long-term antitumor responses. For this purpose, pharmacokinetic (PK) and pharmacodynamic (PD) data were acquired from a preclinical study applying systemic IL-21 therapy in murine solid cancers. We developed an integrated disease/PK/PD model for the IL-21 anticancer response, and calibrated it using selected “training” data. The accuracy of the model was verified retrospectively under diverse IL-21 treatment settings, by comparing its predictions to independent “validation” data in melanoma and renal cell carcinoma-challenged mice (R2>0.90). Simulations of the verified model surfaced important therapeutic insights: (1) Fractionating the standard daily regimen (50 µg/dose) into a twice daily schedule (25 µg/dose) is advantageous, yielding a significantly lower tumor mass (45% decrease); (2) A low-dose (12 µg/day) regimen exerts a response similar to that obtained under the 50 µg/day treatment, suggestive of an equally efficacious dose with potentially reduced toxicity. Subsequent experiments in melanoma-bearing mice corroborated both of these predictions with high precision (R2>0.89), thus validating the model also prospectively in vivo. Thus, the confirmed PK/PD model rationalizes IL-21 therapy, and pinpoints improved clinically-feasible treatment schedules. Our analysis demonstrates the value of employing mathematical modeling and in silico-guided design of solid tumor immunotherapy in the clinic

Left common carotid artery arising from the brachiocephalic trunk: a case report

An abnormal origin of the left common carotid artery from the initial portion of the brachiocephalic trunk was found in the superior mediastinum in a 81-year-old Caucasian male cadaver during dissection practice. We report on the exact morphology of that variant that is appeared in an incidence of 0,2% in the literature. We discuss the relative literature and pay attention on the significance of such a variation for clinicians in its recognition and protection

Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

The Local Optima Level in Chemotherapy Schedule Optimisation

In this paper a multi-drug Chemotherapy Schedule Optimisation Problem (CSOP) is subject to Local Optima Network (LON) analysis. LONs capture global patterns in fitness landscapes. CSOPs have not previously been subject to fitness landscape analysis. We fill this gap: LONs are constructed and studied for meaningful structure. The CSOP formulation presents novel challenges and questions for the LON model because there are infeasible regions in the fitness landscape and an unknown global optimum; it also brings a topic from healthcare to LON analysis. Two LON Construction algorithms are proposed for sampling CSOP fitness landscapes: a Markov-Chain Construction Algorithm and a Hybrid Construction Algorithm. The results provide new insight into LONs of highly-constrained spaces, and into the proficiency of search operators on the CSOP. Iterated Local Search and Memetic Search, which are the foundations for the LON algorithms, are found to markedly out-perform a Genetic Algorithm from the literature

Damage to the Superficial Peroneal Nerve in Operative Treatment of Fibula Fractures: Straight to the Bone? Case Report and Review of the Literature

Ankle fractures are a significant part of the lower extremity trauma seen in the emergency department. Neurologic complications of ankle fracture surgery are infrequently described but account for significant morbidity. The risk of nerve injury is increased for the Blair and Botte type B pattern of the intermediate cutaneous dorsal nerve branch, crossing the distal fibula from posterior to anterior (at 5 to 7 cm from malleolar tip). This pattern is present in about 10% to 15% of patients. Injuries to the superficial peroneal nerve and its branches negatively influence the outcome. Early recognition and protection might reduce the incidence of superficial peroneal nerve injuries during open reduction and internal fixation of lateral malleolus fractures. We describe 2 surgically treated ankle fractures with superficial peroneal nerve branch (intermediate cutaneous dorsal nerve) involvement and review the current literature